Enantiomerization and hydrolysis of (+/-)-7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide by stopped-flow multidimensional high-performance liquid chromatography.
A novel stopped-flow multidimensional HPLC (sf-MD-HPLC) procedure has been developed to investigate simultaneously the effect of the pH on the enantiostability and hydrolysis of (+/-)-7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide [(+/-)IDRA21]. It was possible to determinate the rate constants and free energy barriers of enantiomerization and hydrolysis rate constants of (+/-)IDRA21, by using two chiral stationary phases (CSPs) and one achiral C18 column. A classical batchwise kinetic method was used to calculate rate constants of hydrolysis at the same temperature and in the same buffers used in sf-MD-HPLC. The good agreement of the results obtained validate the sf-MD-HPLC procedure. Furthermore, hydrolysis rate constants of (+/-)IDRA21 were calculated in a series of buffers over a pH range of 1.20-10.60 at 37 degrees C in order to evaluate the influence of the pH on hydrolysis.
Cannazza
Giuseppe
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, Via Campi 183, 4100 Modena, Italy. cannazza.giuseppe@unimore.it
Carrozzo
Marina M
MM
Braghiroli
Daniela
D
Parenti
Carlo
C
D001581:Benzothiadiazines / Q000737:chemistry*; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013696:Temperature
D001581:Benzothiadiazines; D002021:Buffers